Quizartinib for Newly Diagnosed <i>FLT3</i> -Internal Tandem Duplication–Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II QUIWI Study
Abstract
PURPOSE Quizartinib, an oral, selective, second-generation, type-II FMS-like tyrosine kinase 3 (FLT3) inhibitor with high binding affinity to internal tandem duplication (ITD) and wild-type (WT) FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3 -ITD–negative AML. The phase III QuANTUM-First trial showed that quizartinib significantly prolonged survival versus placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3- ITD–positive AML. We investigated the safety and efficacy of quizartinib in patients with ND FLT3 -ITD–negative AML. METHODS The phase II, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients age 18-70 years with ND FLT3 -ITD–negative (mutant-to-WT allelic ratio <0.03) AML. Patients were randomly assigned 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg once daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary end point was event-free survival (EFS). Secondary end points included overall survival (OS) and safety. RESULTS Overall, 273 patients were randomly assigned to quizartinib (n = 180) or placebo (n = 93). At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively ( P = .046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively ( P = .012); 3-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis. CONCLUSION The addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3 -ITD–negative AML.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (61)
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Eduardo Rodríguez-Arbolí
Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS/CSIC), University of Seville, Seville, Spain
Jose Luis López-Lorenzo
Maria Isabel Gómez-Roncero
Eva Barragan
Rosa Ayala
HOSPITAL 12 DE OCTUBRE, MADRID, Spain
Carmen Chillon
17Hospital Universitario de Salamanca, IBSAL, Salamanca, Spain
María José Calasanz
7Genetics Department, CIMALAB Diagnostics, Clínica Universidad de Navarra, Pamplona, Spain
Bruno Paiva
Blanca Boluda
7Hospital Universitari i Politecnic La Fe, Valencia, Spain
Ignacio Casas-Avilés
Pilar Lloret-Madrid
3Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Laida Cuevas
José Ángel Raposo-Puglia
Alfonso Fernandez
1St. Jude Children's Research Hospital, Dept. of Hematology, Memphis, United States
David Martinez-Cuadron
2Hospital Universitario La Fe, Valencia, Spain
Víctor Noriega
Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
Jesús Lorenzo Algarra Algarra
Carmen Botella
Hematology Department. Hospital General Universitario Dr. Balmis, Alicante, Spain
Maria Jose García Perez
Hospital Universitario Torrecárdenas, Almeria, Spain
Susana Vives
18Hospital U. Germans Trias i Pujol ICO Badalona, Badalona, Spain
Olga Salamero
13Hospital U. Vall D'Hebron, Barcelona, Spain
Olga Arce
Jorge Labrador
1Hospital Universitario de Burgos, Burgos, Spain
Juan Miguel Bergua
Inmaculada Marchante Cepillo
Raimundo García Boyero
Josefina Serrano
University Hospital Reina Sofia. IMIBIC. UCO, Cordoba, Spain
Matxalen Olivares
Carlos Rodríguez-Medina
Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas De Gran Canaria, Spain
Antonio Romero Aguilar
María Solé Rodriguez
32Hospital Universitario Juan Ramón Jiménez, Huelva, Spain., Hematology Department, Huelva, Spain
Juan Antonio López-López
16Hospital Universitario de Jaén, Jaén, Spain
Maria-José Sánchez
Carmen Martínez-Chamorro
Marta Polo
6Hospital Universitario Clinico San Carlos, Madrid, Spain
Pilar Herrera Puente
16Hospital Ramón y Cajal, Madrid, Madrid, Spain
Maria Calbacho
1Hospital 12 de Octubre, Hematology and Hemotherapy, Madrid, Spain
José Luis López Lorenzo
12Hospital Fundación Jiménez Díaz, Madrid, Spain
Irene Sánchez-Vadillo
Alfonso Fernández Fernández
Manuel Barrios
Antonio Martínez-Francés
Teresa Bernal
3Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
M. Carmen Mateos
Hospital Universitario de Navarra, Navarra, Spain
María Lourdes Amador Barciela
38Complejo Hospitalario Pontevedra, Pontevedra, Spain., Hematology Department, Pontevedra, Spain
María-Belén Vidriales
13Hospital Universitario de Salamanca, Salamanca, Spain
Mercedes Colorado
Hospital Universitario Marqués de Valdecilla, Santander, Spain
Natàlia Alonso
Adrian Mosquera
1Health Research Institute of Santiago de Compostela, Computational and Genomic Hematology (GrHeCo-Xen), Santiago de Compostela, Spain
Jose Antonio Perez Simon
13Hospital Universitario Vírgen del Rocío, Sevilla, Spain, Sevilla, Spain
Iryna Luts Khoroz
34Hospital Nuestra Señora del Prado, Talavera de la Reina, Spain
Bernardo Javier González
Maria Isabel Gomez Roncero
16Complejo Hospitalario de Toledo, Toledo, Spain
Rebeca Rodriguez-Veiga
2Hospital Universitario La Fe, Valencia, Spain
Mar Tormo
Hospital Clinico Universitary. INCLIVA Research Institute, Valencia 46010, Spain
Maria Jose Sayas
Rebeca Cuello
Sandra Suárez
Laida Cuevas Palomares
Maria Teresa Olave